Leveraging The Body's Healing Ability With Silk

Serica Technologies relies on bioengineering and textile engineering to develop and customize its silk fibroin-based scaffolds and grafts to optimize their function.

By Janet Bealer Rodie, Associate Editor

T extile materials and textile engineering are increasingly valued in the biotechnology
field, as more and more textile-based products are developed for such applications as tissue
engineering and implantation within the body to help it heal and restore function where tissue has
been damaged or destroyed. Both biodegradable and nonbiodegradable fibers may be used to lend their
particular properties, depending on the intended application; and knitted, woven and nonwoven
structures have been developed for very specialized products that take advantage of particular
structural properties.

Silk, which has a centuries-long history of medical use as a suture, is the fiber of
choice for products under development at Serica Technologies Inc., a Medford, Mass.-based medical
device developer and manufacturer of natural silk fibroin-based biomaterials using advanced textile
engineering and biomedical production technologies. Serica plans to offer the materials as
commercial, off-the-shelf nonmammalian, long-term bioresorbable grafts and scaffolds that can be
implanted using standard reconstructive surgical procedures to provide support for regenerating
ligaments, tendons and other connective tissues, ultimately helping the tissue return to full
functionality. Its principal product is the SeriACL™ graft for use in anterior cruciate ligament
(ACL) repair, but the company’s overall scope covers not only orthopaedic and sports medicine, but
also aesthetic and plastic surgery as well as drug delivery solutions.

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According to Dr. Gregory H. Altman, the company’s founder, president and CEO, use of
the SeriACL graft would eliminate the need to harvest tissue from the patient to repair the
ligament, which not only would speed recovery, but also would reduce the cost of the procedure.
Preclinical trials on animals have demonstrated the success of SeriACL as well as Serica’s
SeriCuff™ scaffold, an implant for rotator cuff tendon repair. Clinical trials on humans
are underway in Europe, and Altman expects to commercialize the products overseas by the beginning
of 2009. Serica hopes to initiate US trials next year as well.

Serica Technologies' silk fibroin-based
SeriACL™ graft (top) is intended to replace tissue harvested from the patient to repair
the anterior cruciate ligament (ACL) of the knee, providing a base (bottom) to be infiltrated with
native cells and remodeled into functional tissue.

Quest For A Better SolutionAltman became interested in developing the silk fibroin-based biomaterials after he
injured his ACL while playing football for Tufts University and endured a lengthy, arduous
rehabilitation following reconstructive surgery. After graduation, he went on to earn a doctorate
in biotechnology engineering at Tufts. In 1998, while pursuing his doctoral studies, he founded
Serica Technologies, originally called Tissue Regeneration Inc., with his professor, Dr. David
Kaplan — chair of Tufts’ Department of Biomedical Engineering and director of its Biotechnology
Center — and Dr. John C. Richmond — chair of the Department of Orthopaedics at Boston-based New
England Baptist Hospital and the surgeon who repaired Altman’s ACL — to develop products based on
technology Altman and Kaplan were developing at Tufts. The Serica-Tufts connection continues, and
Altman also servesas a research assistant inthe university’s departmentsof Biomedical Engineering and Orthopaedics.

The Advantages Of SilkSerica has developed proprietary processes for bioengineering standard
Bombyx mori silk to purify it and make it bioresorbable. “Silk is a unique protein that is
made of very simple basic amino acids that the body can metabolize, but it also offers unparalleled
mechanical strength,” Altman said.

“Synthetic polymers bioresorb independently from the body’s healing process. A
protein-based material such as silk, following our bioengineering of it, bioresorbs as a function
of the body’s healing process,” he said as he explained the advantages of silk over man-made
materials. He added that a graft made from a man-made polymer and seeded with cells to regenerate
tissue begins to bioresorb immediately, before the body is able to provide blood to new tissue, and
the inflammation present following surgery is not conducive to cell growth.

Off-the-shelf mammalian collagen, also used as a basis for regenerating native
tissue, presents other challenges in the post-surgical environment, Altman said. “Off-the-shelf
collagen available as a scaffold material is not native functional collagen, and in many instances
it lacks the mechanical properties needed by an ACL scaffold, for example. Mammalian collagen is
much more susceptible to breakdown in that inflamed joint following surgery and goes away too
quickly; and it doesn’t offer enough strength,” he explained.

In contrast, Altman said, silk fibroin has the strength to survive the three-month
avascular period. Once blood begins to flow to the affected area, the body’s own healing process
begins to take over, infiltrating the graft with native cells and remodeling it into functional
tissue. “At that point, the body itself can begin to break down the SeriACL graft,” he said.

“Our ultimate goal is to have the body create its own functional collagen,” he
continued, explaining that following surgery, the ligaments become incased in their own synovial
tissue over time. “Once the graft is encased, you have a healthy growth environment within that
tissue to restore functional collagen. The concept is to simply take advantage of what the body
already knows how to do — in this instance, it just needs a little bit of help getting there. This
is what the SeriACL graft is intended to do.”

Preclinical trials in goats implanted with the SeriACL graft demonstrated the
efficacy of the silk-based biomaterial: 95 percent of the animals returned to normal gait by six
months, and the graft structure was permeated by regenerated ligament and bioresorbed by 12 months.
In another trial involving implantation of the SeriCuff scaffold in sheep, the animals returned to
a normal gait by six days on average, and repair strength at three months improved by 42 percent
compared with traditional rotator cuff repair strength.

Engineering The StructureBeyond the silk fibroin, the textile structure also is critical to final product
design. “It’s not only the micromaterial that the cell will see, but also the structure that
determines the rate at which the body can penetrate the graft in order to heal,” Altman
said.

Through textile engineering, the company has customized its various products to
support specific healing rates according to where the graft or scaffold is to be implanted.

Altman bioengineered the silk fibroin in the laboratories at Tufts, but Tufts does
not have a textile engineering department, and the bioengineering department does not include
mechanical engineering. “The textile development was done at Serica — that’s one reason we formed
the company,” Altman said, noting that he worked with textile engineering students and professors
from schools such as the University of Massachusetts – Dartmouth. Serica’s staff now includes four
textile engineers, and seven product and process engineers who have helped develop the company’s
final products.

“We saw the potential in a particular biomaterial, silk. When faced with the
macro-level design challenges of engineering a particular body part or tissue type, we turned to
textile engineering,” he explained. “We have explored all the way from yarn production through 3-D
knitting. We went from bioengineering the protein component of the fiber to understanding yarn
dynamics and the appropriate types of designs that control the strength, elasticity and fatigue
life of the material — all properties critical in tissue engineering. Once we understood the yarn
properties, the next challenge was the tissue or scaffold structure. To translate the yarn
properties to the body, that’s where the fabric engineering components have come in.”

After exploring a variety of standard yarn-manufacturing techniques, Altman and his
team incorporated several of them into a semi-custom process in order to achieve the final product
properties. As for the fabrics, described as 3-D engineered textiles with both knit and crochet
elements, the manufacturing techniques — also customized according to the required properties of
each end product — create an organized, open scaffold that the cells can penetrate, while
maximizing silk’s mechanical strength.

Developing the processes and end products has involved hands-on experimentation by
the company’s staff, figuring out as they went along what would work and what wouldn’t.

“We’ve really had to rely on a variety of engineering inputs to solve the problems,”
Altman said. “We’re taking standard textile techniques and adapting them to create a structure that
will be most receptive by the body. It’s really taking textile engineering to the next
level.

“In almost everything we’ve done, we’ve had to rely significantly on our own
expertise,” he continued. “We needed to have our biomedical engineers and mechanical engineers in
front of the machines to work hand-in-hand with the textile engineers as different fabric
formations were created. That back-and-forth led to an understanding of how we might be able to
achieve our goals.”

Early on, Altman and his team realized they wouldn’t find what they needed in
standard machinery or textile format. Through their collaborations, Serica’s engineers have in one
instance designed machinery specifically to do what is required. In other cases, the company has
worked with the machinery manufacturer to adapt standard equipment to its needs.

Engineers operate one of the multiple types of knitting machines in Serica's controlled
manufacturing environment.

Facility And OperationSerica recently expanded its facility to total 26,000 square feet of research and
development, manufacturing and administrative space. Of its 30 employees, 20 are biomedical,
textile and mechanical engineers, and scientists. The company plans to add four new manufacturing
positions over the next year as it ramps up its manufacturing operation in preparation for
commercializing its products.

The 8,000-square-foot manufacturing operation comprises a controlled, continuously
monitored environment, most of which is dedicated to the textile operation. Materials allowed in
that environment are limited; and controls are in place to remove oils, dust and other contaminants
from the machines, many of which have been used only to process Serica’s own materials, thus
eliminating chances of cross contamination. Altman said the controlled environment facilitates the
company’s efforts to uphold high levels of cleanliness similar to those found in clean
rooms.

The company has implemented its own quality control system in order to provide
continuous feedback to its textile engineering team. It also has entered its first preliminary
audit for certification to the ISO 13485 standard, which specifies quality management system
requirements for the manufacture of medical devices. Altman hopes to receive certification by
the end of the first quarter of 2008.

Serica has received funding from both public and private sources to help it set up
its operation and develop its processes and products.

“You have to take control of the manufacturing process, but to implement that for a
medical device is certainly a resource-intensive endeavor,” Altman said. “I can’t set up in a
factory — I have to set up in a controlled environment because our materials are designed to
survive the rest of their lives in a patient’s body.”

Early funding came from the National Institutes of Health, the National Science
Foundation, the American Orthopaedic Society for Sports Medicine, and friends and family; but a
grant from the National Institute of Science and Technology (NIST) in 2004 was key in terms of
textile engineering developments.

“The NIST grant really propelled us into textile engineering functionality,” he
said. “The grant is given to companies to take on high-risk programs, and via their support we were
able to expand our expertise in textile engineering so we could develop our SeriCuff scaffold. That
funding led to venture capital financing for $5 million. In February 2007, we closed another round
for $12 million.”

Altman believes the biomedical field offers good opportunities for textile
engineering students. “I hope people can realize its value in biotechnology such that we keep the
academic programs strong,” he said.

Serica's Product Line

Serica’s core orthopaedic products are the
SeriACL™ graft for anterior cruciate ligament (ACL) repair and the
SeriCuff™ scaffold for rotator cuff tendon repair. For plastic surgery applications, it is
developing the
SeriFascia™ surgical scaffold, a general mesh designed to support body wall reconstruction
and plication; and
Eplica Fascia™ customized scaffolds to support the face, neck, breast or abdominal wall
beneath the skin surface.

The company also is developing
SeriGel™ and
Eplica Silk™ injectable hydrogels, derived from silk fiber dissolved into a water-based
solution, for tissue repair. Serica is able to control the gels’ viscosities, mechanical properties
and the way they bioresorb in the body.